There has been a steady increase in the number of cases of syphilis in the United States since the middle 1980s, with a dramatic rise in incidence among heterosexual men and women and of congenital syphilis. There also have been changes in geographic distribution of cases and an association with cocaine use. The ophthalmologic manifestations of syphilis are broad. There is anecdotal evidence that the natural history of syphilitic infection is altered by coinfection with human immunodeficiency virus. The potential of coinfection with HIV makes the clinical evaluation, treatment, and assessment of therapeutic outcome of syphilitic infection more confounding and controversial. This article provides a review of the changing demographics and ophthalmic manifestations of syphilis, the current status of laboratory testing techniques, and management approaches to various types of ocular syphilis.